HETEROCYCLES

■ Contents

■ Synthetic Utilities of o-Phenylenediamines: Synthetic Approaches for Benzimidazoles, Quinoxalines and Benzo[1,5]diazepines

Magdy Ahmed Ibrahim*

*Department of Chemistry, Faculty of Education, Ain Shams University, El-Maqreezy St, Roxy, Heliopolis, Cairo 11711, Egypt

Abstract

This review represents the methods developed for the synthesis of benzimidazoles, quinoxalines and benzo[1,5]diazepines from the condensation of o-phenylenediamines with a variety of electrophilic reagents.

■ Synthetic Access to Azolylthiazoles

Bakr F. Abdel-Wahab,* Hanan A. Mohamed, Abdelbasset A. Farahat, and Kamal M. Dawood

*Applied Organic Chemistry Department, National Research Center, Dokki, Giza, Egypt

Abstract

Published data over the last years on the methods of synthesis and biological applications of azolylthiazoles are reviewed here for the first time till 2011. The review was classified according to the type of azole ring linked to thiazole.

■ Intrinsic Fluorescence of 1,3-Benzoxazinephanes

Rodolfo Quevedo* and Cesar A. Sierra

*Chemistry Department, Faculty of Science, Universidad Nacional de Colombia, Ciudad Universitaria, Carrera 30 # 45-03, Bogotá, Colombia

Abstract

A new 1,3-benzoxazine nuclei-based fluorescent system is presented. The photophysical aspects are briefly discussed. The results suggested that the presence of oxazinic methylenes is necessary for fluorescence to be present.

■ Efficient and Mild Procedure for the Decarboxylative Cyanomethyl Esterification of Arylmalonic Acids Using ClCH2CN/1,8-Diazabicyclo[5.4.0]undec-7-ene

Niiha Sasakura, Tomoyuki Yamauchi, Keiji Nakano, Yoshiyasu Ichikawa, and Hiyoshizo Kotsuki*

*Laboratory of Natural Products Chemistry, Faculty of Science, Kochi University, 2-5-1, Akebono-cho, Kochi 780-8520, Japan

Abstract

An efficient and mild procedure for the decarboxylative cyanomethyl esterification of arylmalonic acids has been developed. The reaction can be performed at room temperature by using chloroacetonitrile and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in toluene, and the desired arylacetic acid cyanomethyl esters are obtained in high yields within a short period of time.

■ Alternative Synthesis of Radioiodinated Trisaccharide Derivatives, 2-(4-125Iodophenyl)ethyl 2-Acetamido-2-deoxy-β-D-glucopyranosyl-(1→2)-α-D-mannopyranosyl-(1→6)-β-D-glucopyranoside, and Preparation of Its Analogs Having Different Lengths of Alkyl Chains Instead of Ethyl Group: Acceptor Substrates of N-Acetylglucosaminyltransferase V for in vivo Imaging

Kenji Arimitsu, Tetsuya Kajimoto, Hiroyuki Kimura, Masahiro Ono, Minoru Ozeki, Manabu Node, Yoshiro Ohmomo, Hideo Saji,* and Masayuki Yamashita*

*Kyoto Pharmaceutical University, 5 Misasagi-Nakauchi, Yamashina, Kyoto, Japan

Abstract

A radioiodinated artificial substrate of N-acetylglucosaminyl- transferase V (GnT-V), 2-(4-iodophenyl)ethyl 2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→2)-α-D-mannopyranosyl-(1→6)-β-D-glucopyranoside ([125I]1a), was alternatively synthesized by using the glycosylation reaction from the non-reducing end, in which a glycosyl sulfoxide and a thioglycoside were employed as the glycosyl acceptor and donor, respectively. In addition, two derivatives of [125I]1a having different lengths of alkyl chain ([125I]1b, [125I]1c) were prepared in the same way to increase the permeability of the substrates through the cell membrane and into the Golgi apparatus, where GnT-V acts to modify glycoconjugates by transferring N-acetylglucosamine units from UDP-GlcNAc.

■ 7-O-Methylated Anthocyanidin Glycosides from the Reddish Purple Flowers of Catharanthus roseus ‘Equator Lavender’

Kenjiro Toki, Norio Saito, Mika Kitaura, Fumi Tatsuzawa,* Atsushi Shigihara, and Toshio Honda

*Laboratoryof Olericultural and Floricultural Science, Faculty of Agriculture, Iwate University, 3-18-8 Ueda, Morioka, Iwate 020-8550, Japan

Abstract

Four new anthocyanins (pigments 1 – 4) were isolated from the reddish purple flowers of Catharanthus roseus ‘Equator Lavender’, and identified to be hirsutidin 3-O-[6-O-(α-rhamnopyranosyl)-β-galactopyranoside]-5-O-galactopyranoside as pigment 4, and 3-O-[6-O-(α-rhamnopyranosyl)-β-galactopyranoside]s of 7-O-methylpetunidin as pigment 2, of 7-O-methyldelphinidin as pigment 3, and of hirsutidin as pigment 1 by chemical and spectroscopic methods. It is noteworthy that the findings of 7-O-methylpetunidin of pigment 2 and 7-O-methyldelphinidin of pigment 3 are the first report in plants. Furthermore, hirsutidin 3-O-[6-O-(α-rhamnopyranosyl)-β-galactopyranoside] of pigment 1 was observed as a main anthocyanin in the reddish purple flower of this plant.

■ One-Step Synthesis of Tetrazolo[1,5-a]pyrimidines by Cyclization Reaction of Dihydropyrimidine-2-thiones with Sodium Azide

Xi-Cun Wang,* Ying Wei, Yu-Xia Da, Zhang Zhang, and Zheng-Jun Quan

*Gansu Key Laboratory of Polymer Materials, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, Gansu 730070, China

Abstract

An novel, versatile and cost-effective approach for tetrazolo[1,5-a]pyrimidines and tetrazolo[1,5-a]quinazolines from cyclization reaction of dihydropyrimidinethiones with sodium azide in the presence of mercuric acetate is described. To compare this procedure with the conventional method, we carried out the cyclization reactions through direct functionalization of the pyrimidinethione core, which obtained from Biginelli 3,4-dihydropyrimidine-2-thiones or 4-aryl-7,7-dimethyl-5-oxo-1,2,3,4,5,6,7,8- octahydroquinazoline-2-thiones.

■ Dihydroazamacrosphelides: Synthesis and Apoptosis Inducing Activities

Kenji Sugimoto, Yuta Kobayashi, Takashi Kondo, Naoki Toyooka, Hideo Nemoto, and Yuji Matsuya*

*Graduate School of Medicines and Pharmaceutical Sciences for Research, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan

Abstract

Dihydroazamacrosphelides, which were aza-analogues of 3-epi macrosphelide L, were prepared according to ring-closing metathesis strategy. Their biological assay revealed that the oxidized diketo-analogues showed stronger apoptosis inducing activity than their dihydroxy precusors.

■ Studies on the Synthesis of Nicotinamide Nucleoside and Nucleotide Analogues and Their Inhibitions towards CD38 NADase

Zhe Chen, Anna Ka Yee Kwong, Zhenjun Yang, Liangren Zhang,* Hon Cheung Lee, and Lihe Zhang

*National Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Road, Beijing 100083, China

Abstract

Nicotinamide adenine dinucleotide (NAD) analogues inhibit the NADase activity of CD38. In the current study, efficient protocols for the synthesis of substituted-nicotinamide nucleosides and nucleotides were developed. The one-pot phosphorylation–esterification strategy provides a convenient way of obtaining nicotinamide nucleoside phosphodiesters from the corresponding nucleosides. Structure–activity relationship information revealed that replacement of 3’-hydroxy group with F or N3 led to the considerably decrease of activity as compared with ara-F NMN. Phosphodiesterification of nicotinamide nucleosides lowers their inhibitory activities in some extent.

■ Synthesis of N-(3-Cyano-7-ethoxy-1,4-dihydro-4-oxoquinolin-6-yl)acetamide

Qiang Zhang, Yongjun Mao, Zheng Liu, Kai Xie, Yi Zhu, Yabing Wei, Xiangrui Jiang,* and Jingshan Shen

*Chinese Academy of Sciences, Shanghai Institute of Materia Medica, 555 Zuchongzhi Rd., Zhangjiang Hi-Tech Park, Shanghai, 201203, China

Abstract

New route for the preparation of N-(3-cyano-7-ethoxy-1,4- dihydro-4-oxoquinolin-6-yl)acetamide (1), a key intermediate for the synthesis of selective EGFR kinase inhibitors, was described.

■ Two New Flavones from Uvaria macrophylla Roxb. var. microcarpa and Their Cytotoxic Activities

Zhong Chen, Xue-Run Liu, Yan-Li Liu, Qiong-ming Xu,* and Shi-lin Yang

*School of Pharmacy, Soochow University, Suzhou 215123, China

Abstract

Two new flavones, macrophyllains A and B, were isolated from the leaves of Uvaria macrophylla Roxb. var. microcarpa, and their structures were established on the basis of their spectral data. The two new compounds showed some cytotoxic activity by MTT assay.

■ One-Pot Synthesis of 2-Nitrooxyalkoxylated Inosine Analogs Using Cyclic Ether and Isoamyl Nitrite

Norikazu Sakakibara, Masahiro Komatsu, and Tokumi Maruyama*

*Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki City, Kagawa, 769-2193, Japan

Abstract

An O6-methylguanosine derivative (1) was treated with isoamyl nitrite in the presence of a cyclic ether such as trimethylene oxide, tetrahydrofuran, or tetrahydropyran to give the corresponding 2-nitrooxyalkoxy-6-methoxypurine riboside derivatives (2a–c).